AppropriationsUpdate from Capitol Hill

Last month, Congress passed H.R. 6157, the fiscal year (FY) 2019 appropriations "minibus" bill comprised of the Labor, Health and Human Services (HHS), Education bill and the Department of Defense bill. The House passed the bill by a vote of 361-61, following Senate passage by an overwhelming margin of 93-7. President Trump signed the bill into law Sept. 28.

The package, which includes $39.1 billion (a $2 billion increase) for the National Institutes of Health (NIH), also includes $6.14 billion for the National Cancer Institute. With the enactment of this bill, the NIH has now received its fourth consecutive and significant annual increase in funding, a boost of 30 percent ($9 billion) above the budget in FY 2015. Advocates across the medical research community have cheered the funding increase as a victory for patients and all Americans.

Moreover, the bill's passage marks the first time since 1996 that the Labor HHS bill has been enacted on time and that the NIH has not been subject to a continuing resolution (CR) into a new fiscal year. In a remarkable return to "regular order," Congress has now cleared 87 percent of federal funding for FY 2019. H.R. 6157 includes a CR through Dec. 7 for the remaining appropriations bills that have not been passed, and thus avoids a government shutdown. Among the bills still awaiting passage is the FY 2019 Agriculture, Rural Development, Food and Drug Administration (FDA) and Related Agencies appropriations bill. Like the Labor HHS bill, the bill that funds the FDA also is part of a "minibus" package with other spending bills. As a result, the FDA will be held at FY 2018 levels until the bill can be resolved later this year. Both the House and Senate Ag/FDA bills proposed significant increases to the FDA's base budget, and they both included funding of $20 million for the FDA Oncology Center of Excellence, an increase of $5 million over current levels.

Rally for MedicalResearch Brings Advocates Together
in Support of NIH

-By Brandon L. Leonard, MA

The sixth Annual
Rally for Medical Research was held Sept. 12-13 in Washington, D.C. The AACR,
the founding organizer and a lead sponsor of the rally, joined nearly 350 organizations to advocate for robust,
sustained, and predictable annual funding increases for the National Institutes
of Health (NIH).

Patient advocates, caregivers, researchers and health
professionals from 30 states gathered for an advocacy training on Sept. 12
before attending the Rally for Medical Research reception. Speakers at the
reception included NIH Director Francis Collins, MD, PhD; Senators Roy
Blunt (R-Missouri) and Patty Murray (D-Washington);
and Representative
Kevin Yoder (R-Kansas).

On Sept. 13, Representative
Jamie Raskin (D-Maryland) gave remarks at a breakfast for
Rally participants before they left for Capitol Hill to meet with nearly 200
Congressional offices. The advocates expressed their appreciation to Senate
offices for passing a bill with a $2 billion funding increase for the NIH in
fiscal year (FY) 2019, while requesting that the House of Representatives
support the Senate-passed funding level of $39.1 billion for the NIH in the
final FY 2019 Labor-HHS-Education Appropriations Bill.

In addition to all those attending meetings on
Capitol Hill, many more advocates participated in the Rally National Day of
Action, also held Sept. 13. Individuals and organizations across the country
contacted their members of Congress via phone, email, and social media to urge
their support for a $2 billion increase for the NIH in FY 2019.

The Rally for Medical Research initiative was
launched in April 2013 to bring together the entire medical research community
to ask Congress to make the NIH a national priority. Through the annual Hill
Day, the Rally for Medical Research continues to raise awareness about the
critical need for an increased investment in the NIH to improve health, spur
progress, inspire hope, and save more lives.

To
see the brief video that was shown at the rally breakfast, please visit the Rally website. Photos from the 2018 rally will also be posted
to the website in the coming weeks.

AACR ReleasesCancer Progress Report 2018

-By Brandon L. Leonard, MA

The AACR released its Cancer Progress
Report 2018 Sept. 12 at a congressional briefing in Washington, D.C. The
report highlights how federally funded research discoveries are fueling the
development of new and even more effective ways to prevent, detect, diagnose,
and treat cancer.

At the briefing, AACR CEO Margaret Foti,
PhD, MD (hc) provided welcome remarks and Congressman Ted Poe (R-TX), who was
featured in the report, spoke of his own cancer story and how it has influenced
his work as a member of Congress. Panelists included AACR President Elizabeth
M. Jaffee, MD, Quynh-Thu Le, MD, of the Stanford Cancer Institute, and three
cancer survivors whose stories were included in the report: Chuck Dandridge,
Laurie Trotman, and Tori Lee, who attended with her parents, Dana and Chris.

The report, now in its eighth edition,
is a cornerstone of the efforts of the AACR to educate the public about cancer
and the importance of biomedical research, as well as to advocate for increased
federal funding for the NIH, NCI, and FDA. This year’s report chronicles how
federally-funded research continues to improve lives, and it shows that our
ability to fully capitalize on our ever-growing knowledge of cancer is
dependent on robust, sustained, and predictable federal funding. The report
highlights how recent advances across the clinical cancer care continuum, in
particular immunotherapy and molecularly-targeted therapies, are helping cancer
patients and their families. This year’s report also focuses on the continued
challenges we face in addressing cancer health disparities and cancer
survivorship.

Progress and Promise AgainstCancer: A Biden Cancer Community Event

Since the launch of Vice President Biden's "national commitment to end cancer as we know it," AACR members and leaders have worked to shape and realize the vice president's vision.

-The following is an excerpt from a blog posted Sept. 25, 2018 by Eileen Glanton Loftus

Editor's note: Progress and Promise Against Cancer is the AACR's initiative to educate the public about cancer and cancer research. This event is part of a live and online event series that has occurred in communities across the nation.

Jill Biden can tell when a parent has lost a child.

"I can spot them," she said. "The curve of their shoulders, as if they can feel the arms of a small child wrapped around their necks. Though we are strangers, we understand the untellable truths about one another."

Dr. Biden and her husband, former Vice President Joe Biden, lost their son Beau to glioblastoma, an aggressive brain cancer, in 2015. Beau's death galvanized them to launch the Biden Cancer Initiative, a mission to accelerate progress in cancer prevention, detection, diagnosis, research, and care.

The Biden Cancer Initiative convened a national Biden Cancer Summit on Friday, with an anchor event in Washington, D.C., and approximately 450 events in other U.S. locations. Dr. Biden delivered the keynote address at Philadelphia's event, Progress and Promise Against Cancer, which was jointly hosted by the American Association for Cancer Research (AACR) and WHYY, Philadelphia's NPR and PBS station.

Featuring some of Philadelphia's leading cancer researchers, the summit provided an opportunity to take stock of recent advances in cancer prevention and treatment, while looking ahead to the next wave of progress.

Over the course of the day, both Vice President and Dr. Biden returned frequently to one theme: "the urgency of now." That urgency underpinned Dr. Biden's emotional keynote speech.

"For the researchers, thank you for the work you do every single day. To the patients and the survivors, thank you for your courage and hope. Joe and I are with you every day," she said.

The AACR is pleased to announce that Dr. Norman (Ned) E. Sharpless, director of the National Cancer Institute (NCI), will be the keynote speaker at the AACR Science of Cancer Health Disparities conference in New Orleans. The purpose of the conference is to advance the understanding of, and ultimately help to eliminate, the disparities along the cancer continuum that represent a major public health problem in our country. Learn more about the conference and register.

AACR ApplaudsFDA’s New Steps to Address Epidemic of Youth E-cigarette Use

Public health experts have declared the rising prevalence of youth e-cigarettes use a public health epidemic. On Sept. 12, 2018, the FDA announced a series of historic enforcement actions aimed reducing this dangerous trend and preventing another generation from becoming addicted to nicotine.

FDA Public Workshop:Patient-focused Drug Development Guidance for Clinical Outcome Assessments

On Oct. 15-16, the U.S. Food and Drug Administration (FDA) is hosting a two-day public workshop to entitled, “Methods to Identify What is Important to Patients and Select, Develop or Modify Fit-for-Purpose Clinical Outcome Assessments.” The FDA is seeking information and comments from a broad range of stakeholders.

I-SPY 2 TRIALDemonstrates Promise of Master Protocols

-By Trevan Locke, PhD

In September, the I-SPY 2 TRIAL presented an update of the trial's progress and showcased the exciting potential of master protocols in trial design at the National Press Club in Washington, D.C. I-SPY 2 is the longest running adaptive platform trial and has a goal of personalizing treatment for individual early-stage breast cancer patients.

Instead of a conventional "one drug, one trial" approach, I-SPY 2 uses a master protocol developed with the U.S. Food and Drug Administration (FDA) that allows it to test multiple treatments in parallel and add or remove treatment options as data are collected. Patients are assigned to treatment arms by an algorithm utilizing Bayesian decision rules based on images of their tumors and biomarker data. Primary treatment is given before surgery. Since the trial's inception in 2010, over 1,300 patients across the U.S. have entered the trial and 17 drugs will have been a part of the trial by the end of 2018. Seven of those drugs have graduated from the trial with two receiving accelerated approval from the FDA and another gaining breakthrough designation. The trial has also shown that lack of all signs of cancer in tissue samples following primary treatment, known as pathologic complete response (pCR), is a strong early predictor of long-term outcomes. Using pCR as a surrogate endpoint allows for earlier evaluation of therapies compared to traditional endpoints. "This is the future of clinical trials for many reasons, but the best news is that it is preventing disease progression, curing more patients, and brings the best of what we learn in research to clinical care," said Anna Barker, PhD, cochair of the I-SPY 2 Project Oversight Group and director of Transformative Healthcare Networks at Arizona State University.

Master protocols are generally organized into three types. Umbrella trials are used to study multiple therapies for a single disease, while basket trials are used to study a single therapy for multiple diseases. I-SPY 2 falls into the third category, platform trials. Like umbrella trials, platform approaches look at multiple therapies in the context of a single disease, but can continually enroll patients across multiple treatment arms and have treatments added to or removed from the trial as new data points are collected. These protocols offer common screening platforms that benefit drug developers, through shorter, more streamlined recruitment processes, and patients, by providing more and earlier access to potentially beneficial therapies. Additionally, centralized governing bodies are used to oversee the trials and provide consistent decisions throughout the trial across multiple therapies. These innovations are not without cost; they require significant up-front time, planning, and coordination to establish trial infrastructure and bring involved parties together. Expertise and funding from federal agencies will be important to overcoming such challenges and effectively scaling the innovative approach of I-SPY 2 to future trials.

On Sept. 28, the agency released draft guidance to industry to drive continued discussion on the design and conduct of master protocol trials for the evaluation of cancer therapies highlighting the importance of such innovative trial designs in advancing patient-centered care in an efficient manner.

The Ninth Annual Congressional Childhood Cancer Summit was
held Sept. 14 on Capitol Hill. The event featured remarks from National
Cancer Institute (NCI) Director Dr. Ned Sharpless and provided an opportunity
to discuss recent legislative victories in childhood cancer as well as next
steps. Rep. Michael McCaul (R-TX), founder of the Congressional Childhood
Cancer Caucus, made opening remarks along with fellow co-chair Rep. Mike Kelly
(R-PA). Reps. Jackie Speier (D-CA) and G.K. Butterfield (D-NC) are also co-chairs
of the caucus.

This year’s passage of the Childhood Cancer Survivorship, Treatment,
Access and Research (STAR) Act was one of the legislative achievements
highlighted at the summit. Before the end of the event, Rep. McCaul announced
that the House and Senate had reached a conference agreement to fully fund the
STAR Act in fiscal year (FY) 2019, another significant win for childhood cancer
advocates.

During his remarks, Dr. Sharpless focused on some of the areas where he
sees great promise in combatting childhood cancer, including breakthroughs in
immunotherapy and the power of big data. He provided updates on the Cancer
Moonshot and noted that the STAR Act would provide new tools for the NCI to
utilize in its work on childhood cancer. He also praised Congress’ continued
bipartisan commitment to medical research, as evidenced by the $2 billion
increase for the National Institutes of Health (NIH) approved for FY 2019.

The summit was followed by a luncheon and art exhibit sponsored by the
Alliance for Childhood Cancer, of which the AACR is a member. Copies of the
newly released AACR Cancer Progress Report 2018 were made available to
attendees at the event.

The summit was one of many events taking place in September in
recognition of Childhood Cancer Awareness Month. On Sept. 13, the Alliance
for Childhood Cancer, the Coalition Against Childhood Cancer (CAC2), and The
Leslie Carson Foundation hosted the Golden Toast, a celebration of legislative
achievements and an opportunity to recognize both congressional champions and
advocates in the childhood cancer community. CureFest for Childhood Cancer,
held Sept. 15-16, was a weekend full of family-friendly activities with
a rally, a candlelight vigil, a walk, games, activities and live entertainment.
CureFest aims to increase awareness of childhood cancer and make it a national
priority by bringing together families and advocates from across the country.

Defining GeneTherapy – Semantics Affect Regulation

Beth Oates is a PhD candidate in the Department of Microbiology, Immunology and Molecular Genetics at the University of Kentucky, College of Medicine, Lexington, Kentucky. Her research focuses on the bacterial competition and community interactions effect on pathogenicity.

Genes are organized sections of DNA within each cell that contain the information for when the cell should divide, grow, and function, but with scientific discoveries such as DNA that encodes small noncoding RNA, it is becoming harder to completely define 'genes.' Therefore, it is no surprise that the definition of gene therapy is also subject to debate. Although definition disputes seem like mere semantics, definitions play a critical role in scientific communication, but also in requirements and regulations for products that are marketed as gene therapies.

There have been several efforts to define gene therapy since the discovery of DNA's structure, but the modern definition dates back to 1993 in an official notice by the U.S. Food and Drug Administration (FDA) that aimed to clarify the agency's authority to regulate these therapies. At that time, gene therapy was defined as therapies used to "modify or manipulate the expression of genetic material or to alter the biological properties of living cells." This definition was broad enough to ensure that the FDA retained oversight over a then-new and advancing technology and it remains the definition today.

A variety of approaches are being studied in cancer-focused gene therapy research, including genetically engineered viruses that directly kill cancer cells, gene transfer to alter the abnormal functioning of cancer cells, and immunotherapy such as chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is unique in that gene expression is altered outside the patient's body. In this therapy, a sample of a patient's own immune T-cells is collected, and new genes are incorporated into the cells' DNA. Expression of the new genes causes the T-cells to target tumor cells. Once T-cells are genetically engineered into CAR T-cells, these newly equipped CAR T-cells are then infused back into the patient to seek out and destroy tumor cells while also proliferating to generate more cancer-killing cells. Through such approaches, gene therapies are poised to be critical tools for cancer treatment.

Given the diverse approaches to "gene therapy" in cancer and other disease areas, it is important to consider if the scientific community is defining it appropriately. Past definitions, such as that proposed by the Institute of Medicine in 1986 in which the replacement of somatic DNA with exogenous DNA is required, were too specific resulting in definitions for gene therapy that only encompass a fraction of modern therapies. For example, the IoM definition of gene therapy would exclude CRISPR therapies that can edit somatic DNA without the need for exogenous genetic material. However, broader definitions may include too many therapies. The FDA's definition of altering gene expression could be interpreted to encompass small molecule drugs or even changes to diet or sleeping — all of which can change what genes a cell expresses. A recent commentary on defining gene therapies proposed defining a gene therapy "as the intentional, expected permanent, and specific alteration of the DNA sequence of the cellular genome, for a clinical purpose." This definition would encompass permanent modifications that are reversible through further modification, mutations in either germline or somatic cells, as well as therapies in which modifications can occur not just inside a patient's body, but outside of the body, as with CAR-T. Furthermore, the definition requires the intent to alter a specific gene which would distinguish true gene therapy from other therapies that have a secondary effect on gene expression.

As more products seek FDA approval as gene therapies, the importance of clearly defining gene therapy is critical, not only for the semantics of science, but for helping regulators clarify incentives and requirements for those products appropriately characterized as gene therapy.

Capitol Corner:AACR Interviews Members of Congress

Every month, the AACR will be interviewing members of Congress to get their personal story and views on cancer research. This month, we are featuring interviews with Congressman Ted Poe (R-Tx) and Congressman Mark DeSaulnier (D-Ca) from the Cancer Progress Report 2018.

Congressmen Poe and DeSaulnier are co-chairs of the Congressional Cancer Survivors Caucus. Each of them graciously shared their personal cancer story as part of the report.